Our group is interested in understanding the role of cytokines in the development of autoimmune diseases. This year we made progress in understanding old observations as well as discovering new, exciting mechanisms in B cell biology. Specifically, are studying the role of tumor necrosis factor (TNF) in both autoimmune models of lupus as well as in human autoimmune disease. We now understand why mice that are deficient in TNF develop anti-nuclear autoantibodies (ANA), but very rarely develop kidney disease. My students, Rachel Robbins and Carolyn Karafiath found that although loss of TNF drives autoantibody production that deposit in kidneys, no lymphocytic inflammation occurs due to the loss of TNF (which is a pro-inflammatory molecule). These data have important implications in the treatment of rheumatic diseases with drugs that inhibit TNF?s actions. Recently, we have turned our attention to a newly discovered cytokine, termed ?IL-21?. This protein is secreted only by activated CD4 T cells, and known to be important in T cell and NK cell activity. We have found that it also plays a critical role in B cell maturation and development. We have turned our attention to it?s possible role in autoimmune disease by studying how it may be involved in animal models of lupus as well as in human systemic lupus erythematosus and Rheumatoid arthritis. Lastly, Anna-Marie Fairhurst, a post-doctoral fellow, is investing the role of the Toll-like receptors (TLR) in the development in various murine models of SLE as well as in human B cell biology. She has found that TLR9 is differentially expressed on distinct human B cell populations which may suggest a role for this molecule in controlling B cell maturation and have important implications in human disease. Using mice deficient in TLR9 expression she is studying its possible role in controlling B cell maturation and development as well as its role in autoimmune disease. Our group is dedicated to understanding how cytokines are contributing to the development of systemic lupus erythematosus and rheumatic diseases. We feel that our research will lead to new therapeutics as well as to understanding the mechanisms of basic B cell biology.